Inadequate kidney function can be an implication of various diseases, disorders, and trauma situations, and millions of people worldwide rely on renal replacement therapy for their survival. Dialysis, either through the peritoneal membrane or from the blood (i. e. hemodialysis) is a critical tool in the treatment of patients presenting with acute renal failure, but the technique is equally important for maintenance treatment of patients with chronic kidney diseases of various types and origins. Indications necessitating dialysis include inter alia severe retention of products not wasted by impaired kidneys, for instance urea, creatinine, uric acid, potassium, and phosphate, but also fluid overload, or even acute drug poisoning, to name a few.
Hemodialysis can be carried out either as an outpatient or as an inpatient therapy, but careful monitoring and surveillance is nevertheless pivotal irrespective of the situation, as numerous side effects and complications, both immediate and long-term, are associated with the procedure. These effects are sometimes dictated by the different types of hemodialysis access methods utilized, but the dialysis procedure per se is also associated with certain inherent risks, normally requiring both staff surveillance and automatic monitoring.
Hemodialysis is performed using two separate circuit systems, one circuit carrying the blood from the patient and another carrying dialysis fluid, a solution comprising mineral ions, for removal of waste substances, as well as water, from the blood. The principle behind dialysis is diffusion over a semipermeable membrane, i. e. the dialysis filter, which interconnects the two circuit systems. The blood drawn from the patient (either from an arterio-venous access or from a central dialysis catheter) enters an arterial tube and is subsequently, using a blood pump, flushed into a dialysis filter, where waste products are being removed. The cleansed blood is returned to the patient through the venous part of the tubing. However, despite being a substantially closed circuit, air is constantly leaking in to the blood flow, either as a result of leakage at the watertight connection sites, or as an implication of air present in the circuit prior to starting the dialysis.
As a result of the potentially detrimental effects of air entering the blood stream and subsequently the body, the blood circuit system is carefully monitored through the use of infrared and/or ultrasound safety control systems. The risks associated with entry of large air bubbles into the blood stream has been a long-standing concern within the dialysis field, as a resultant emboli could potentially be lethal to the patient undergoing the renal replacement therapy. Hence, substantial research efforts have been directed towards improving detectors for dialysis monitoring and surveillance, as well as towards developing various types of devices for air removal within the system. An important factor behind the development of systems for improved air removal is the consensus within the research community with regards to the importance of bubble size and the leakage of air as a function of time (Polaschegg, Artificial Organs, 31, 911-912, 2007). The apparent insignificance of microbubbles, i. e. bubbles exhibiting sizes around 100 μm, has been attributed to the collapse and subsequent blood absorption of small bubbles. Additionally, the lungs are considered to function as barriers for bubbles with diameters above 20 μm, and this paradigm, together with the perceived practical impossibility of preventing microbubble entry, today dictates the industry standards.
The venous part of the dialysis system is normally arranged with a venous chamber enabling removal of larger amounts of air present within the system, but such a chamber is only effective in separating bubbles of a relatively large size. As a result of the industry standpoint with regards to microbubbles, these types of air removal systems have been deemed adequate for clinical use. Nevertheless, there is substantial clinical evidence for air emboli passing the venous chamber, which is meant to act as an air trap for larger air bubbles, without activating the alarm (Jonsson, P., et al., “Air bubbles pass the security system of the dialysis device without alarming”, Artif Organs, (2007), 31(2): 132-9). Extensive data collected by the inventors of the present invention show that these microbubbles pass into the vessels of the patient (Forsberg, U., et al., “Microemboli, developed during haemodialysis, pass the lung barrier and may cause ischaemic lesions in organs such as the brain”, Nephrol Dial Transplant, (2010), Epub ahead of print), and that the presence of these emboli increase significantly within the arterial system, including the carotic artery (i. e. the main artery for supply to the brain), after start of the dialysis.
Besides an increased incidence of pulmonary damage by venous emboli, arterial microemboli contribute to the increased prevalence of cerebral atrophy and regression of neurocognitive status, especially in long-term dialysis patients, indicating a significant need for improved devices for separation of microbubbles as well as larger bubbles of air.
Venous chambers constituting the current art are normally arranged as vertical drip chambers with the inlet at a high point and the outlet at a low point, in order for large bubbles, i. e. bubbles with a buoyancy force overcoming the drag force from the flow, to ascend vertically upwards. Modified versions include devices designed so as to promote a circulatory flow in the chamber or devices with various types of geometric appearance, for instance substantially cubic shapes.
WO 2006/030263, for instance, discloses a blood chamber for use in an extracorporeal circuit comprising a blood inlet port, a blood containment chamber, and a first conduit. The chamber is arranged with a relatively large segment for slowing down the blood flow and separate gases from the blood, forming an overlying gaseous zone.
As a result of the current paradigm, the venous chambers in the art are constructed to eliminate merely relatively large bubbles, and do not remove microbubbles (i. e. bubbles with sizes under 50-400 μm) at all. Generally, many devices provide very blunt tools for gas separation and numerous devices in fact promote air contamination. Neither are the devices for gas removal specifically adapted to non-Newtonian and relatively viscous fluids such as blood, where elimination of eddies and currents are intrinsically critical. Further, the prior art generally overlook the biological properties of blood, often resulting in coagulation in slow-flowing parts, including filters in connection with stagnant flow or air retention, or corners of the utilized devices, having a negative impact both on the removal of air bubbles but also on the dialysis as such.
Furthermore, devices of the prior art generally exhibit very complex configurations comprising multiple parts, resulting in manufacturing difficulties and an increased risk of air leakage.